A groundbreaking study led by researchers at University College London (UCL) in collaboration with the global diagnostics company Veracyte has unveiled a powerful molecular test that could transform treatment strategies for men with advanced prostate cancer. Prostate cancer remains one of the most formidable challenges in oncology, particularly when the disease has metastasized and conventional therapies often yield unpredictable results. This study, recently published in the renowned journal Cell, reveals that a gene expression test performed on routinely collected prostate tissue can precisely identify which patients with metastatic prostate cancer are most likely to benefit from the chemotherapy drug docetaxel. Such personalized insights promise to extend patients’ lives while sparing others from the debilitating side effects of ineffective treatment.
The test at the heart of this breakthrough, known as the Decipher Prostate Genomic Classifier, is an advanced molecular diagnostic tool that evaluates patterns of gene expression across a wide spectrum of cancer-related genes. By deciphering the tumor’s transcriptome, this test categorizes tumors into distinct risk profiles that correlate with treatment sensitivity and overall prognosis. While this test has been widely utilized in the United States for localized prostate cancer to predict the likelihood of progression, this study represents the first compelling evidence from a randomized clinical trial that it can also guide treatment decisions in patients whose cancer has spread beyond the prostate itself.
Central to the research was data from the STAMPEDE trial, a landmark phase III randomized controlled study that enrolled over 1,500 men diagnosed with advanced prostate cancer. These participants were treated with androgen deprivation therapy (ADT), which is designed to suppress male hormones like testosterone that fuel cancer growth. The STAMPEDE trial subsequently tested the addition of multiple therapies, including abiraterone and docetaxel chemotherapy, examining their ability to improve survival outcomes over a median follow-up period of 14 years. The depth and duration of this trial allowed the research team to undertake a comprehensive molecular analysis, correlating gene expression profiles with long-term clinical outcomes.
Crucially, the researchers focused on a subgroup of 832 patients with metastatic prostate cancer. Analysis revealed a striking divergence in survival benefits linked to the Decipher Prostate scores. Patients with high Decipher scores exhibited a remarkable 36% reduction in risk of death after receiving docetaxel chemotherapy, a benefit starkly contrasted with those exhibiting low scores who saw less than a 4% risk reduction. This differential response underscores the value of molecular profiling as a precision medicine approach, enabling oncologists to tailor treatments based on the intrinsic biology of each patient’s tumor rather than a one-size-fits-all strategy.
Chemotherapy with docetaxel, while capable of prolonging survival, often comes at the expense of patients’ quality of life due to significant side effects such as fatigue, neuropathy, and immunosuppression. Therefore, the ability to pre-identify patients unlikely to benefit spares them from unnecessary toxicity and offers clinicians the option to explore alternative therapies or supportive strategies. This represents a seminal advancement in the treatment paradigm for metastatic prostate cancer, where prediction and personalization have long been elusive.
The collaboration between UCL and Veracyte was essential to making this test accessible and validated in a clinical context. UCL’s expertise in cancer biology and clinical trial design paired with Veracyte’s capabilities in high-throughput gene expression profiling drove this innovation from concept to commercial availability. Moreover, beyond the Decipher test, the collaborative effort uncovered several novel molecular classifiers that have predictive value for patient outcomes and therapeutic responses, suggesting a broader landscape for future biomarker-driven treatment adjustments.
Further molecular insights emerged from the identification of a signature indicating inactivity in the tumor suppressor gene PTEN, a gene well-known for its role in regulating cell growth and survival. This PTEN inactivity signature was associated with both shorter survival when treated with hormone therapy alone and a greater benefit from chemotherapy. This dual predictive capacity sharpens the precision with which clinicians can stratify patients, emphasizing the intricate molecular interplay underpinning prostate cancer progression and treatment responsiveness.
Leading the scientific endeavor, Professor Gert Attard of UCL expressed optimism about the future impact of these findings. The integration of molecular profiling into clinical decision-making heralds a new era where chemotherapy can be individualized, improving outcomes and minimizing harm. This approach promises to revolutionize care and aligns with the broader trend in oncology towards treatment personalization driven by genomic insights rather than solely clinical staging or histopathology.
The significance of this advancement is further highlighted by epidemiological data: prostate cancer accounts for approximately 55,100 new cases annually in the UK, and it remains the second leading cause of cancer death among men, with 12,000 fatalities projected in the current year alone. Most deaths arise from cases initially diagnosed at advanced or metastatic stages, underlining the urgent need for refined therapeutic strategies tailored to individual tumor biology. The Decipher Prostate test, therefore, offers a real-world, clinically actionable tool to improve survival and quality of life on a large scale.
Prostate Cancer UK, Cancer Research UK, and several charitable foundations played key roles in funding this research, enabling the extensive clinical and molecular analyses required for such a landmark study. The STAMPEDE trial itself, a beacon of innovation in prostate cancer research, continues to foster discoveries that translate into improved standards of care for men with advanced disease states, fulfilling its mission to identify new, more effective therapies.
Dr. Emily Grist of the UCL Cancer Institute emphasized that this research represents a milestone in the molecular reclassification of prostate cancer. By dissecting tumors into distinct transcriptional subtypes predictive of treatment response, the study moves the field towards bespoke therapeutic regimens. Future clinical paradigms may involve biopsies routinely subjected to transcriptomic profiling, followed by matched treatment pathways that can dynamically evolve with emerging molecular data, ensuring patients receive the most effective and least harmful therapies available.
From a commercial and translational perspective, UCL Business (UCLB) has facilitated the transfer of these scientific insights into market-ready diagnostics. Their collaboration with Veracyte exemplifies how academic discoveries can be harnessed to yield real-world impact. The availability of the Decipher Prostate test in the US as a reimbursed clinical assay stands as a testament to the successful bridging of fundamental research and patient care, setting a blueprint for future biomarker-driven precision oncology.
In conclusion, the integration of transcriptome-wide molecular classifiers into therapeutic decision-making for advanced prostate cancer represents a transformative leap forward. This approach enables the identification of patients likely to derive meaningful survival benefits from docetaxel chemotherapy while sparing others from unnecessary toxicity. As further molecular signatures and classifiers are elucidated, including those involving PTEN inactivity, the future of prostate cancer treatment promises to be increasingly personalized, precise, and effective, embodying the modern principles of precision medicine.
Subject of Research: People
Article Title: Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers
News Publication Date: 27-Aug-2025
Web References:
References:
10.1016/j.cell.2025.07.042 (DOI link to the publication in Cell)
Keywords: Prostate tumors, Molecular profiling, Advanced prostate cancer, Gene expression, Chemotherapy sensitivity, Decipher Prostate Genomic Classifier, STAMPEDE trial, Personalized medicine
